Rosuvastatin calcium is known by its chemical name as bis[(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt of formulae (1)
which is known to inhibit the HMG-CoA reductase, and subsequently suppress the biosynthesis of cholesterol. Rosuvastatin calcium is useful in the treatment of hypercholesterolemia, hyperlipoproteinemia, and atherosclerosis. Rosuvastatin calcium may form hydrates with a varying content of water.
EP-A1-0 521 471 describes in example 7 the preparation of rosuvastatin calcium in powder form. Rosuvastatin sodium is dissolved in water at room temperature and an aqueous calcium chloride solution is added dropwise. The collected precipitate is an amorphous powder. U.S. Pat. No. 6,777,552 discloses the preparation of rosuvastatin calcium through hydrolysation of methyl 7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxy-(E)-6-heptanoate with calcium hydroxide in a water/ethanol solution. The compound is not isolated from the solution to characterize an amorphous or crystalline state.
In WO 00/42024 is disclosed a crystalline form, hereafter referred to as form A of bis[(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt and hydrates thereof, which are prepared by dissolving the amorphous form in a mixture of water and an organic solvent such as acetone or acetonitrile under heating and then cooling the solution to precipitate crystalline form A.
Crystalline forms often show desired different physical and/or biological characteristics which may assist in the manufacture or formulation of the active compound, to the purity levels and uniformity required for regulatory approval. Crystalline forms of such active compounds may also possess improved pharmacological characteristics, for example, improved bioavailability, and therefore, novel crystalline forms offer enhanced possibilities to modulate and design improved drug products. There exists therefore a need for other crystal forms than form A of bis[(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt to have a sufficient diversity on crystalline materials to optimize manufacture, formulation and biological efficiency.